Critical point drying is a process to remove liquid, e.g. water, in a controlled way from a sample. It is commonly used to remove water, e.g. from biological samples in the preparation for scanning electron microscopy and in the production of microelectromechanical systems (MEMS).
Critical point drying exploits the property that fluids exhibit a supercritical state if temperature and pressure are above the critical point, where no phase boundary between liquid and gas exists. If the transition from liquid to gas is performed via the supercritical regime, damaging or a collapse of the delicate sample is avoided due to the absence of detrimental surface tension of the liquid.
For water the critical point is at a temperature of 374° C. and a pressure of 22.06 MPa. The high critical temperature makes it inconvenient to directly perform critical point drying on an aqueous sample since it would cause heat damage. Hence a transitional fluid is used, usually liquid carbon dioxide (CO2) which has a critical temperature of 31° C. and a critical pressure of 7.39 MPa. However, CO2 is not miscible with water, therefore an intermediate fluid is used in an intermediate step to dehydrate the sample before performing critical point drying with CO2. Commonly used intermediate fluids are acetone, ethanol, isopropanol, amyl acetate, or a solution of one of those in water.
Typically a critical point drying process contains the following steps:                Transporting the dehydrated samples in the intermediate fluid into a chamber under ambient pressure. The chamber may partly be filled with intermediate fluid to avoid the surface of the sample becoming touch dry.        Replacing the intermediate fluid in the chamber with the transitional fluid.        Transferring the transitional fluid from liquid to supercritical state by heating and pressurising the chamber. Meanwhile a part of the transitional fluid is drained from the chamber to avoid excessive overpressure.        Transferring the supercritical transitional fluid to the gaseous state by slowly depressurising the chamber and letting the gas escape while heating to avoid recondensation of the transitional fluid. Finally the chamber is at ambient pressure, and the sample can be removed.        
With common systems the step of dehydrating the sample by means of the intermediate fluid is performed in a separate vessel, mostly manually, before transporting the sample into the chamber. The amount of intermediate fluid and time is chosen according to empirical values, which leads to a high consumption of intermediate fluid and a long process duration in order to make sure that the sample is sufficiently dehydrated.
After dehydration the sample is manually transferred to the chamber. Since the sample should not be in contact with surrounding air, careful handling has to be applied with dedicated transport vessels.
In order to ensure sufficient replacement of the intermediate fluid by the transitional fluid, large amounts of transitional fluid are flowed through the chamber, and additional rest periods may be interposed to improve diffusion of the intermediate fluid out of the sample. The parameters of this process are again chosen according to empirical values and lead to a high consumption of transitional fluid and a long process duration.